Sjogren's syndrome (SS) is a clinical and scientific challenge. This application will focus on the role of B cells n this disorder, because B cells seem to play a key role in the pathogenesis of the illness and because B cell directed therapy for SS and related disorders is an important new approach. The broad goal is to exploit a new SS murine model to isolate the role of the B cell in SS. We will characterize B cell subsets in diseased tissue compare their repertoire to peripheral B cells using molecular genetic techniques. We will develop means of depleting B cells in vivo using monoclonal antibodies so that we will have a model of human SS B cell depletion (currently in clinical trials), and will examine the B-cell repertoire during reconstitution of depleted animals. Finally, we will develop in vivo B-cell imaging techniques in SS mice to study real-time trafficking of B cells. These methods may prove useful to monitor disease activity and therapy in humans with SS and related conditions. The research is relevant to the agency mission of understanding and treating this important autoimmune disorder.